Fatty acid profile of phospholipids and sphingomyelin in milk and regulation of sphingomyelin synthesis of mammary glands in cows receiving increasing levels of crushed sunflower seeds.

The objective of this study was to investigate the effect of increasing dietary supplementation of crushed sunflower seed (CSS) in the diet of dairy cows on the fatty acid (FA) composition of phospholipids and sphingomyelin in milk, and on mammary transcription of genes that are important for sphingomyelin de novo synthesis. Four groups of 6 cows received diets supplemented with CSS at 0% (control), or 5, 10, or 15% of dry matter for a 5-wk experimental period. Milk samples and mammary biopsies were collected at the end of the experiment. Phospholipid concentration in milk fat decreased linearly with CSS supplementation. Sphingomyelin concentration in milk fat was unaffected by CSS supplementation. Daily yield of phospholipids decreased linearly with CSS supplementation. Daily yield of sphingomyelin was not significantly affected. The CSS supplementation linearly increased the proportion of monounsaturated FA in milk phospholipids. The major isomer incorporated into phospholipids was C18:1 (n-9 cis), which showed a linear increase with CSS supplementation. The C22:0 proportion in sphingomyelin increased linearly with CSS supplementation and constituted between 15.2 to 25.4% of total FA in sphingomyelin. However, CSS supplementation linearly decreased C23:0 sphingomyelin. Mammary transcription of serine palmitoyl transferase, long chain subunit 1 and subunit 2, the rate-limiting enzymes in ceramide synthesis, showed a linear decrease with increasing CSS supplementation. In conclusion, the data showed that dietary supplementation of CSS linearly increased the proportion of unsaturated FA and monounsaturated FA in milk phospholipids with no effect on phospholipid concentration. In addition, CSS supplementation linearly decreased n-3 polyunsaturated fatty acid proportion in sphingomyelin. The results further showed that mammary transcription of important genes for sphingomyelin de novo synthesis is regulated by lipid supplementation.

Gastrointestinal metabolism of phytoestrogens in lactating dairy cows fed silages with different botanical composition.

Dietary phytoestrogens are metabolized or converted in the gastrointestinal tract of ruminants, only limited knowledge exists on the extent and location of this conversion in vivo. The objective of this study was to quantify the gastro-intestinal metabolism of phytoestrogens in lactating dairy cows fed silages with different botanical composition. Four lactating rumen cannulated Norwegian Red cattle were assigned to a 4 × 4 Latin square with 1 cow per treatment period of 3 wk. The 4 treatment silages were prepared from grasslands with different botanical compositions: organically managed short-term timothy (Phleum pratense L.) and red clover (Trifolium pratense L.) ley (2 yr old: ORG-SG); organically managed long-term grassland with a high proportion of unsown species (6 yr old; ORG-LG); conventionally managed perennial ryegrass (Lolium perenne L.) ley (CON-PR); and conventionally managed timothy ley (CON-TI). The herbages were cut, wilted, and preserved with additive in round bales, fed as a mix of the first and third cut at 90% of ad libitum intake, and contributed to 70% of the total dry matter intake. Milk, feed, omasal digesta, urine, and feces were collected at the end of each period and analyzed for the concentrations of phytoestrogens by using a liquid chromatography-tandem mass spectrometry technique. Concentration of total isoflavones was highest in ORG-SG and lowest in CON-TI silage, whereas the content of total lignans was highest in the grass silages. The isoflavones were extensively metabolized in the rumen on all diets, and the recovery of formononetin and daidzein in omasum, mainly as equol, averaged 0.11 mg/mg. The apparent intestinal metabolism was less severe as, on average, 0.29 mg/mg of the omasal flow was recovered in feces. The plant lignans were also strongly degraded in the rumen. However, the flow of lignans to omasum and excretion in feces were, on average, 7.2- and 5.2-fold higher, respectively, than the intake of the plant lignans matairesinol and secoisolariciresinol, known as precursors of mammalian lignans. Thus, excretion to milk could not be directly related to intake, implying that plant lignans other than matairesinol and secoisolariciresinol in forage are precursors for enterolactone production in the rumen and for its content in milk. Equol followed mainly the flow of large particles out of the rumen, whereas the mammalian lignans were distributed between phases proportional to dry matter flow. The main metabolism of phytoestrogens occurred in the rumen and the main route of excretion was through feces and urine, with only a small part being excreted in milk. The concentration of phytoestrogens in milk can be manipulated through intake but the intermediate transfer capacity to milk appears to be limited by saturation.

Effects of feeding dairy cows different legume-grass silages on milk phytoestrogen concentration.

Phytoestrogens are hormone-like substances in plants that can substantially influence human health (positively or negatively), and when fed to dairy cows are partly transferred to their milk. The aim of this study was to investigate the effects of varying the botanical composition and regrowth interval of legume-grass silage on phytoestrogen intake and milk phytoestrogen concentrations. In one experiment, 15 Swedish Red dairy cows were fed 2- or 3-cut red clover-grass silage, or 2-cut birdsfoot trefoil-grass silage. In a second experiment, 16 Norwegian Red dairy cows were fed short-term ley silage with red clover or long-term ley silage with white clover, and the effects of supplementation with α-tocopherol were also tested. High concentrations of formononetin and biochanin A were found in all silage mixtures with red clover. The milk concentration of equol was highest for cows on the 2-cut red clover-grass silage diet (1,494 µg/kg of milk). Because of the metabolism of biochanin A, genistein, and prunetin, their concentrations in milk and the apparent recovery were low. Coumestrol was detected in only short-term and long-term ley silage mixtures, and its milk concentration was low. Concentrations of secoisolariciresinol and matairesinol were higher in 2-cut birdsfoot trefoil-grass and long-term ley silage mixtures, those with legume species other than red clover, and the highest grass proportions. The 2-cut birdsfoot trefoil-grass silage diet also resulted in higher enterolactone concentration than the other diets (226 µg/kg of milk). Lengthening the regrowth interval increased the intake of secoisolariciresinol and decreased the recovery of lignans. Feeding long-term ley silage resulted in higher milk lignan concentrations but lower milk isoflavone concentrations than feeding short-term ley silage. The apparent recovery of all phytoestrogens except prunetin was highest on the 2-cut birdsfoot trefoil-grass silage diet. No effect of α-tocopherol supplementation was observed on milk concentrations of any of the measured phytoestrogens. Variations were observed in milk concentrations of phytoestrogens, especially of equol, among cows, which could not be explained by variations in diet composition or phytoestrogen intake. The results show that milk phytoestrogen concentration is strongly influenced by silage botanical composition, but questions regarding phytoestrogen metabolism remain to be answered.

DTI reveals hypothalamic and brainstem white matter lesions in patients with idiopathic narcolepsy.

BACKGROUND: Symptomatic narcolepsy is often related to hypothalamic, pontine, or mesencephalic lesions. Despite evidence of disturbances of the hypothalamic hypocretin system in patients with idiopathic narcolepsy, neuroimaging in patients with idiopathic narcolepsy revealed conflicting results and there is limited data on possible structural brain changes that might be associated with this disorder. METHODS: We investigated with diffusion tensor imaging (DTI) whether microstructural abnormalities in the brain of eight patients with idiopathic narcolepsy with cataplexy are detectable compared to 12 healthy controls using a 1.5T MRI scanner. Whole-head DTI scans were analyzed without an a priori hypothesis. Voxelwise statistical analysis of fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics (TBSS), a non-linear analysis approach. RESULTS: Patients with narcolepsy showed microstructural white matter changes in the right hypothalamus as well as in the left mesencephalon, pons, and medulla oblongata. Additionally, areas in the left temporal lobe, the pre- and postcentral gyrus, the frontal and parietal white matter, the corona radiata, the right internal capsule, and the caudate nucleus had altered microstructure in patients with narcolepsy. CONCLUSIONS: Our study shows widespread microstructural white matter changes that are not visible on conventional MRI scans in patients with idiopathic narcolepsy. In support of the evidence from patients with symptomatic narcolepsy, we found microstructural changes in the hypothalamus, mesencephalon, pons, and medulla oblongata. Changes are in accordance with disturbances of the hypothalamic hypocretin system and its projections to mesencephalic and pontine areas regulating REM sleep.

Bioavailability of marine n-3 fatty acid formulations.

The use of marine n-3 polyunsaturated fatty acids (n-3 PUFA) as supplements has prompted the development of concentrated formulations to overcome compliance problems. The present study compares three concentrated preparations - ethyl esters, free fatty acids and re-esterified triglycerides - with placebo oil in a double-blinded design, and with fish body oil and cod liver oil in single-blinded arms. Seventy-two volunteers were given approximately 3.3g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 2 weeks. Increases in absolute amounts of EPA and DHA in fasting serum triglycerides, cholesterol esters and phospholipids were examined. Bioavailability of EPA+DHA from re-esterified triglycerides was superior (124%) compared with natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%). Free fatty acid bioavailability (91%) did not differ significantly from natural triglycerides. The stereochemistry of fatty acid in acylglycerols did not influence the bioavailability of EPA and DHA.

[Risk scores and outcomes after cholecystectomy: a comparison between a university hospital and a short-stay clinic--a prospective observational study]. / Risikoprofil und Ergebnisqualität nach Cholezystektomie--Ein Vergleich zwischen einer Universitäts- und Praxisklinik.

BACKGROUND: This study was designed to compare the risks of morbidity and mortality of patients in a surgical department of an academic medical centre and a short-stay clinic. Furthermore, economic and patient-related parameters were assessed. METHODS: A number of 50 respectively 33 consecutive patients scheduled for a cholecystectomy were included in this prospective study. Data were collected well-assorted against the POSSUM score, the duration of the operation, complications and the length of stay as well as quality of life and patient satisfaction. RESULTS: No differences among patients of the two hospitals became apparent as they were referenced against the POSSUM score, nor were any discrepancies in expected respectively ex-post complications upon cholecystectomy observed. The continuance of the operative procedure was found to be significantly lengthened in the university hospital as compared with the non-academic clinic (120.1 +/- 34.3 min vs. 65.6 +/- 16.3 min; p < 0.001). The difference in durability splits up in 1.2 days pre-operatively versus 2.4 days post-operatively. In return, the post-operative pain therapy was esteemed much better in the university hospital. CONCLUSION: The POSSUM score is a reliable tool to assess morbidity and mortality in surgical patients. The scores were found to be equal for patients in a university hospital and those in a short-stay clinic. Complications likewisely were equally low in both hospitals. The longer duration of the operation and the higher length of stay revealed structural benefits of the smaller unit. Advantages of the academic centre were found in the standards for pain therapy. The present study is taken both as a reference and as a basis for a fundamental process-redesign to the benefit of involved parties e. g. patients, relatives, staff in the university hospital.

Effects of clover-grass silages and concentrate supplementation on the content of phytoestrogens in dairy cow milk.

A 2 x 2 factorial continuous experiment was conducted with 28 Norwegian Red dairy cows in early lactation to compare milk content of phytoestrogens when feeding ad libitum white clover (WCS) or red clover (RCS) grass silages prepared from the second and third cut without and with 10 kg/d supplementation of a standard concentrate. The cows were offered either RCS or WCS for 88 d (period 1) and thereafter a mixed red clover-white clover-grass silage for 48 d (period 2). Total dry matter intake and milk yield were not affected by forage type but increased with concentrate supplementation. Intake of isoflavones was several times greater in RCS than in WCS, whereas intake of lignans was greater in WCS. Concentrate supplementation reduced the intake of most phytoestrogens. Compared with WCS, RCS diets yielded milk with a greater content of flavonoids, whereas milk from WCS diets had greater contents of the mammalian lignans enterodiol and enterolactone. The content of the isoflavan equol was particularly high in RCS diets. There was no apparent carryover effect of clover type on milk phytoestrogen content because there was no difference in content between the silage treatments 3 wk after the cows were transferred to the same silage diet (period 2). Concentrate supplementation reduced the milk contents of the flavonoids equol, biochanin A, and daidzein and increased the content of mammalian lignans. The effects of silage type and concentrate supplementation on milk contents of the individual phytoestrogens were related to the intake of the compound or its precursor, except for the effect of concentrate on mammalian lignans, for which the intake of the known precursors was also reduced. Overall, this study shows that feeding cows with silage containing red clover increases the milk content of flavonoids at both low and high concentrate supplementation levels, and decreases the content of nonflavonoids such as mammalian lignans, when compared with silage containing white clover. The increased content of phytoestrogens in milk may be important when the health benefits of milk are studied.

A longitudinal study of serum cobalamins and its binding proteins in lactating women.

OBJECTIVE: To examine longitudinal changes in serum cobalamins, transcobalamin (TC) and haptocorrin (HC) during lactation and to investigate the influence of vitamin B12 supplementation on these parameters. DESIGN: A 9-month follow-up study. SUBJECTS AND METHODS: Lactating mothers (N=89) including 23 supplemented with vitamin B12 (1-18 microg/daily), 41 partly supplemented and 25 not supplemented. Blood samples collected 3 weeks (baseline) and 4 and 9 months post-partum were analysed for cobalamins, TC and HC. Both the total concentration and the cobalamin-saturated form (holo) of TC and HC were analysed. RESULTS: No significant differences were observed in serum cobalamins or its binding proteins related to supplementation with vitamin B12 or the duration of lactation. Serum cobalamins remained unchanged from 3 weeks to 9 months post-partum. Total TC (holoTC) (median+/-s.e. pmol/l) decreased between 3 weeks (710+/-23 (85+/-12)) and 9 months (602+/-21 (76+/-11)) (P<0.0001 (P=0.0002)), whereas total HC (holoHC) increased from (422+/-11 (300+/-9)) at 4 months to (455+/-13 (317+/-10)) to 9 months post-partum (P<0.0001 (P<0.0001)). CONCLUSION: We report a decrease in TC and an increase in HC during a 9-month period post-partum. No differences were observed between the vitamin B12-supplemented and the unsupplemented groups. Thus, supplementation with vitamin B12 has no impact on the circulating level of serum cobalamins or its binding proteins in a Danish population of lactating mothers.

Folate and vitamin B12 in relation to lactation: a 9-month postpartum follow-up study.

OBJECTIVE: To investigate the relation between lactation and markers of folate and vitamin B12 (B12) deficiency in women with and without vitamin supplementation. DESIGN: A 9-month follow-up study. SUBJECTS AND METHODS: Blood samples from 91 women, who gave birth to a single healthy child, were collected 3 weeks, 4 and 9 months postpartum and analysed for circulating level of homocysteine (tHcy), methylmalonic acid (MMA), folate and B12. The participants were categorized as exclusively, partly or not breast-feeding dependent on the degree of lactation 4 months postpartum. During follow-up, lifestyle factors were recorded by structured interviews. RESULTS: Among 72 exclusively breast-feeding women, the median (10-90% percentile) tHcy was 5.8 (3.1-8.3) micromol/l 3 weeks postpartum, 6.1 (4.1-10.3) micromol/l 4 months postpartum and 5.3 (3.6-8.7) micromol/I 9 months postpartum. At 9 months postpartum, none of the women breast-fed exclusively. No significant change occurred in the concentration of B12 and folate. Exclusively breast-feeding women without vitamin supplementation had higher median tHcy than supplemented exclusively breast-feeding women 4 and 9 months postpartum (7.0 vs 5.4 micromol/l (P < 0.001) and 5.8 vs 4.5 micromol/l (P = 0.003), respectively). Six women had increased (>15 micromol/l) tHcy; four of these were unsupplemented and exclusively breast-feeding. CONCLUSION: We found no overall indication of depletion of the folate and B12 stores during the lactation period in this population. However, folate-supplemented women had lower tHcy and higher folate levels, suggesting a beneficial effect of supplementation with folate throughout lactation.

Dopamine transporter imaging and SPECT in diagnostic work-up of Parkinson's disease: a decision-analytic approach.

As a diagnostic test for patients with suspected Parkinson's disease (PD), single photon emission computed tomography (SPECT) using [(123)I]FP-CIT tracer has better sensitivity but is more expensive than regular clinical examination (CE). Our objective was to evaluate the clinical and economic impacts of different diagnostic strategies involving [(123)I]FP-CIT SPECT. We developed a decision tree model to predict adequate treatment-month equivalents (ATME), costs, and incremental cost-effectiveness ratio (ICER) during a 12-month time horizon in patients with suspected PD referred to a specialized movement disorder outpatient clinic. In our cost- effectiveness analysis, we adopted the perspective of the German health care system and used data from a German prospective health care utilization study (n = 142) and published diagnostic studies. Compared strategies were CE only (EXAM+), SPECT only (SPECT+), SPECT following negative CE (SINGLE+), and SPECT following positive CE (DOUBLE+). Costs of SPECT amounted to euro;789 per investigation. Based on our model, expected costs (and ATME) were euro;946 (52.85 ATME) for EXAM+, euro;1352 (53.40 ATME) for DOUBLE+, euro;1731 (32.82 ATME) for SINGLE+, and euro;2003 (32.96 ATME) for SPECT+; performance of SPECT was induced in 0%, 54%, 56%, and 100% of the patients, respectively. DOUBLE+ was more effective and less expensive than SINGLE+ or SPECT+; thus these two do not offer reasonable choices. The ICER of DOUBLE+ compared to EXAM+ was euro;733 per ATME gained. In sensitivity analyses, the ICER of DOUBLE+ versus EXAM+ ranged from euro;63 to euro;2411 per ATME gained. Whether the diagnostic work-up of patients referred to a specialized movement disorder clinic with a high prevalence of PD should include [(123)I]FP-CIT SPECT depends on patient preferences and the decision maker's willingness to pay for adequate early treatment. SPECT should be used as a confirmatory test before treatment initiation and limited to patients with a positive test result in the clinical examination. These results should be adjusted to the specific setting and individual patient preferences.

Prevalence of resistance to ampicillin, gentamicin and vancomycin in Enterococcus faecalis and Enterococcus faecium isolates from clinical specimens and use of antimicrobials in five Nordic hospitals.

We determined the species distribution and prevalence of ampicillin resistance, high-level gentamicin resistance (HLGR) and vancomycin resistance among clinical enterococcal isolates from five Nordic laboratories (Bergen, Tromsø, Uppsala, Aarhus and Reykjavik). Isolates represented three different groups: (i) all blood culture isolates from 1999; (ii) consecutive in-patient isolates (maximum 40); and (iii) consecutive outpatient isolates (maximum 40) collected during March to May 2000. Antimicrobial use data were collected at the national and hospital level. A high proportion (31.4%) of Enterococcus faecium was detected among blood culture isolates, in contrast to only 4.2% among isolates from outpatients. Ampicillin resistance was not found in Enterococcus faecalis, in contrast to 48.8% in E. faecium isolates. HLGR rates varied considerably between laboratories (1.1-27.6%). Acquired vancomycin resistance was not detected. There were no significant differences in the prevalences of HLGR between in-patient and outpatient isolates at individual hospitals. A cluster of clonally related ampicillin-resistant and HLGR E. faecium isolates was demonstrated in one of the hospitals. The lowest level of hospital antimicrobial use, the lowest proportion of E. faecium and the lowest prevalence of resistance were observed in Reykjavik. The study showed a relatively low level of resistance in enterococci, as compared with most European countries and the USA. However, there were large differences between hospitals with regard to the relative proportion of E. faecium isolates, their susceptibility to ampicillin and gentamicin, as well as the prevalence of HLGR in E. faecalis isolates. This indicates a potential for further improvement of antibiotic policies, and possibly hospital infection control, to maintain the low resistance levels observed in these countries.

Morbidity from parotid sialography.

OBJECTIVE: Sialography is commonly used for the diagnosis of Sjögren's syndrome, although its invasive nature is often regarded as a serious drawback for routine usage. The aim of this study was to evaluate the morbidity and acceptability of parotid sialography using oil-based contrast fluid. STUDY DESIGN: Twenty-four consecutive sialographic procedures were evaluated in terms of morbidity and the patient's acceptance of the procedure, assessed with a standardized questionnaire. Information was also obtained by recording relevant physical parameters during the procedure. RESULTS: There was good acceptance of the sialographic procedure, and the morbidity was low. No signs of overfilling or false route were observed in any of the sialograms. On average, 0.74 mL of contrast fluid was infused with a velocity of 0.01 mL/s. The whole procedure was completed within 12 minutes. CONCLUSIONS: Parotid sialography appears less invasive than is often thought. It had a low morbidity rate and was well accepted by the patients.

Dietary supplementation with methionine and homocysteine promotes early atherosclerosis but not plaque rupture in ApoE-deficient mice.

Hyperhomocysteinemia is an independent risk factor for atherothrombosis. However, causality is unproven, and it remains unknown whether hyperhomocysteinemia promotes atherosclerosis, plaque rupture, and/or thrombosis. We evaluated the short- and long-term effects of hyperhomocysteinemia on plaque size and structure in 99 atherosclerosis-prone apolipoprotein E-deficient mice. Hyperhomocysteinemia was induced by methionine (Met) or homocysteine (HcyH) supplementation: low Met (+11 g Met/kg food), high Met (+33 g Met/kg food), low HcyH (0.9 g HcyH/L drinking water), and high HcyH (1.8 g HcyH/L drinking water). Met and HcyH supplementation significantly raised plasma total homocysteine levels by 4- to 16-fold above those observed in mice fed a control diet (up to 146.1 micromol/L). Compared with controls, aortic root plaque size was significantly larger in supplemented groups after 3 months (56% and 173% larger in high-Met and high-HcyH, respectively) but not after 12 months. Hyperhomocysteinemia was associated with an increase in the amount of collagen in plaques after both 3 and 12 months. Mechanical testing of the tail tendons revealed no weakening of collagen after 12 months of hyperhomocysteinemia. Many plaques in both control and supplemented mice appeared rupture prone morphologically, but all aortic root plaques and all but 1 coronary plaque had an intact surface without rupture or thrombosis. Thus, diet-induced hyperhomocysteinemia promotes early atherosclerosis and plaque fibrosis but does not, even in the long term, weaken collagen or induce plaque rupture.

Effect of calcium supplements on the oral bioavailability of moxifloxacin in healthy male volunteers.

OBJECTIVE: To investigate the effect of concomitant calcium administration on the pharmacokinetics and tolerability of moxifloxacin. DESIGN: This was a nonblinded, randomised, single dose, crossover study in healthy male volunteers. PARTICIPANTS: 12 healthy male Caucasians (age 24 to 45 years) were enrolled in the study. METHODS: In each of the 2 study periods, each volunteer received a single oral morning dose of moxifloxacin 400mg after an overnight fast. In 1 of the study periods, Ca2+ 500mg (Calcium-Sandoz Forte) was administered immediately before, and 12 and 24 hours after, moxifloxacin (total of 3 doses of Ca2+). The 2 study periods were separated by a washout period of at least 2 weeks. RESULTS: Moxifloxacin was well tolerated throughout the study. There was no difference in the area under the plasma concentration-time curve from zero to infinity [AUCinfinity; geometric mean (SD)] of moxifloxacin [32.2 (1.24) vs 33.0 (1.26) mg/L x h, with vs without Ca2+]. Maximum plasma concentration (Cmax) [2.29 (1.27) vs 2.71 (1.33) mg/L, with vs without Ca2+] slightly decreased by approximately 16% and the time to Cmax [median (range)] tended to be slightly prolonged [2.5 (0.8 to 3) vs 0.9 (0.5 to 2.5) hours, with vs without Ca2+]. CONCLUSIONS: The extent of absorption of moxifloxacin is not affected by concomitant Ca2+ intake, whereas the rate of absorption is slightly reduced, an effect not considered to be of clinical relevance. Hence, moxifloxacin may be administered together with Ca2+ without dosage adjustments or special recommendations.

Adenosine is an agonist of the growth hormone secretagogue receptor.

Growth hormone secretagogues (GHSs) are synthetic compounds that induce GH release in several species, including man. The aim of the current study was to identify hypothalamic GHS receptor (GHS-R) agonists. This led to the discovery of adenosine as a GHS-R agonist. We demonstrate that adenosine as well as the A1 adenosine receptor agonist N6-R-phenylisopropyladenosine (R-PIA) induce calcium responses, with EC50 values of 50 nM and 0.5 nM, respectively, in cells which express recombinant human GHS-R. However, neither compound induces a calcium response in nontransfected cells. Binding experiments show that adenosine and the GHS compound MK-0677 bind to membranes from GHS-R expressing cells with nearly identical Bmax values (2.6 +/- 0.1 x 10(-10) mol/mg protein for adenosine and 2.0 +/- 0.3 x 10(-10) mol/mg protein for MK-0677). However, no binding to membranes from nontransfected cells could be detected. Furthermore, we show that the IC50 values for inhibition of the adenosine, R-PIA, and GHS induced calcium responses by the GHS-R antagonist [D-Arg1, D-Phe5, D-Trp7,9, D-Leu11]-substance P are similar. These findings strongly suggest that adenosine and R-PIA are agonists of the GHS-R. Interestingly, neither adenosine nor R-PIA were able to induce GH release from rat pituitary cells in vitro. The implications of the latter finding is discussed.

Within-person variation of plasma homocysteine and effects of posture and tourniquet application.

BACKGROUND: Frequently, the result of only a single determination of total homocysteine in plasma (P-Hcy) is used to distinguish between the probability of the presence or absence of risk for vascular disease. A prerequisite for the interpretation of a single P-Hcy test is knowledge of the magnitude of within-person variation and the possible effects of preanalytical variables. However, data on within-person variation are still sparse and inconsistent, and data for the effect on P-Hcy of posture and tourniquet application during venipuncture are not available. METHODS: The within-person variation of P-Hcy and the effects of posture and tourniquet application during venipuncture were studied in 24 healthy subjects. The analytical imprecision of our stable-isotope dilution assay was 3.1%. RESULTS: The within-person variation (CV) was 8.1%. Daily supplementation with 0.4 mg of folic acid for 2 weeks produced a small but significant decrease in P-Hcy, but there were no significant changes in within-person variation before and after supplementation. After 30 min in the horizontal posture, P-Hcy declined by 6.3%. A 3-min tourniquet application caused a 2.8% increase of P-Hcy. CONCLUSIONS: Our value for within-person variation is consistent with results from studies reported recently in the literature. A 3-min tourniquet application does not add appreciable variation to the measurement of P-Hcy, but the posture of the subject during venipuncture contributes considerably to the within-person variation. We recommend that blood collection when the patient is in a supine position be avoided.

[An outbreak of Pontiac fever among children and adults following a whirlpool bath]. / Et udbrud af Pontiac-feber blandt børn og voksne efter brug af et spabad.

We investigated an outbreak of fever most likely due to a contaminated whirlpool among nine adults and six children visiting a holiday home. The outbreak was characterized by a high attack rate, short incubation periods, influenza-like symptoms and rapid recoveries typical of Pontiac fever. The children, however, experienced less characteristic symptoms and no sequelae compared to the adults. Evidence and presumptive evidence of Legionella (L) infection was found in eleven cases; in one case by isolation of L. pneumophila serogroup 1, in two cases by positive test for Legionella by PCR and in eleven cases with seroconversion. In contrast, two adult non-users of the whirlpool had no symptoms and no serological evidence of infection. This investigation demonstrates differences between adults and children in the clinical picture of Pontiac fever, furthermore it shows that culture and PCR of tracheal aspirate for legionellae can be used in a hospital setting for rapid diagnosis although their sensitivities are low.

Prominent 85-kDa oligomannosidic glycoproteins of rat brain are signal regulatory proteins and include the SHP substrate-1 for tyrosine phosphatases.

The glycoprotein component in rat brain reacting most strongly with Galanthus nivalis agglutinin (GNA) on western blots migrates as an 85-kDa band. GNA identifies mannose-rich oligosaccharides because it is highly specific for terminal alpha-mannose residues. After purification of this 85-kDa glycoprotein band by chromatography on GNA-agarose and preparative gel electrophoresis, binding of other lectins demonstrated the presence of fucose and a trace of galactose, but no sialic acid. Treatment with N-Glycanase or endoglycosidase H produced a 65-kDa band, indicating that it consisted of about one-fourth N-linked oligomannosidic carbohydrate moieties. High-performance anion-exchange chromatography and fluorescence-assisted carbohydrate electrophoresis indicated that the major carbohydrate moiety is a heptasaccharide with the structure Manalpha1-6(Manalpha1-3)Manalpha1-6(Manalpha1-3) Manbeta1-4Glc-NAcbeta1-4GlcNAc (Man5GlcNAc2). Determination of amino acid sequences of peptides produced by endoproteinase digestion demonstrated that this 85-kDa mannose-rich glycoprotein component contained the SHP substrate-1 for phosphotyrosine phosphatases and at least one other member of the signal-regulatory protein (SIRP) family. The unusually high content of oligomannosidic carbohydrate moieties on these receptor-like members of the immunoglobulin superfamily in neural tissue could be of functional significance for intercellular adhesion or signaling.

An outbreak of Pontiac fever among children following use of a whirlpool.

We investigated an outbreak of fever, most likely due to a contaminated whirlpool, among nine adults and six children residing in a summerhouse. The outbreak was characterized by a high attack rate, short incubation periods, influenza-like symptoms, and rapid recoveries, all features typical of Pontiac fever. However, the children had less-characteristic symptoms than the adults, and they did not have any sequelae. Findings on the children's chest radiographs were unremarkable, and none of the children had leukocytosis. Evidence of Legionella pneumophila infection was found in six cases: in one case by isolation of L. pneumophila serogroup 1 and detection of legionellae by PCR, and in five cases by seroconversion to the clinical isolate. Six additional cases had presumptive evidence of legionella infection, with seroconversion to Legionella micdadei antigen; a PCR assay was also positive for legionellae for one of these cases. In contrast, two adult nonusers of the whirlpool had no symptoms and no serological evidence of infection. Serological testing and cultures for other pathogens, as well as cultures of all environmental samples, were negative. This investigation demonstrates the differences between adults and children with respect to the clinical picture of Pontiac fever; furthermore, it shows that culture and PCR assay of tracheal aspirates for legionellae can be performed in a hospital setting for rapid diagnosis, although the sensitivities of these methods are low.

Systematic analysis and controlling of health care organisations lead to numerical health care improvements.

The EFQM model for organisational excellence is used in the health care sector as a tool to diagnose and assess the starting position for the effective QM programme. Feedback reports cover the fields of acute medical care, rehabilitation and ambulant care and contain strengths areas for improvement. Building on the EFQM feedback reports, the Modular Concept for Quality in Health Care ("Heidelberg Model") improves QM both holistically and specifically by implementing so-called "Modules for Excellence". The implementation process follows principles of project management covering medical, nursing and managing issues and the performance is periodically evaluated against targets. QM projects that are designed in the dichotomic way follow three goals. Organisational diagnosis and therapy lead to numerical health care improvements in "Prevention of nosocomial infections" and "Optimising out-patient treatment". Different assessment approaches lead to a diagnosing feedback report for QM in health care. The Modular Concept for Quality in Health Care ("Heidelberg Model") clusters, priorities, implements and evaluates the organisation's key areas for improvement.